Allogeneic hematopoietic stem cell transplantation is a life-saving procedure for hematopoietic malignancies, marrow failure syndromes, and hereditary immunodeficiency disorders. However, wide application of this procedure is limited by availability of suitably HLA-matched adult donors. Umbilical cord blood (UCB) has being increasingly used as an alternative hematopoietic stem cell source for these patients. To date, over 6000 UCB transplant procedures in children and adults have been performed worldwide using UCB donors. Broader use of UCB for adult patients is however limited by the available infused cell dose. This has prompted intensive research on ex vivo expansion of UCB stem cells and UCB graft-engineering including accessory cells able to improve UCB engraftment and reconstitution and for tissue regenerative potential. Recently, two large European and North American retrospective studies demonstrated that UCB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack HLA-matched adult donors. UCB is anticipated to address needs in both transplantation and regenerative medicine fields. It has advantages of easy procurement, no risk to donors, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite HLA disparity.